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Tumour biomarkers can be useful in predicting the risk of metastases and thus prognosis. Some of them can also have a diagnostic use. The use of serum biomarkers, such as lactate dehydrogenase (LDH) or S100b, is recommended in some guidelines, while the use of other serum biomarkers, such as melanoma inhibitory activity (MIA) and vascular endothelial growth factor (VEGF) is limited due to low specificity and limited clinical usability. DNA point mutations in melanoma represent another important biomarker that can guide patient selection and predict treatment response.
Biomarker | Correlation | Limitation | Laboratory Methodology |
References | |
---|---|---|---|---|---|
Enzymes | LDH | Increased levels with worse prognosis Increased LDH levels with distant metastases are classed as stage IV M1C in AJCC Radiological response to immunotherapy on LDH decrease |
LDH can be elevated in other conditions | Photometric assay | [18][19][21] |
Tyrosinase | May correlate with melanoma relapse | Conflicting results in studies done | RT-PCR | [5][40][41][42][43][44] | |
Secreted proteins/antigens | MIA | Increased levels with advanced disease and worse prognosis | Low specificity in newly diagnosed metastatic melanoma | ELISA | [31][33][32] |
TA90 Antigen | May be an independent predictor for survival, prognosis and recurrence | Can be elevated in inflammatory processes | [5][39] | ||
VEGF | Elevated in advanced stage melanoma Associated with negative immune effects Could be an independent prognostic marker for survival |
Levels can also be elevated in healthy individuals Low sensitivity, specificity and positive predictive value in monitoring |
ELISA, RT-PCR | [34][35][37][38] | |
Osteopontin | May be used in conjunction with S100b to predict relapse of high risk for metastases | Can be found in autoimmune conditions | IHC, TMA | [45][46][47][48] | |
IL-8 | Increased levels with disease stage, survival tumour burden and response to treatment | Can be elevated in other inflammatory processes | ELISA, IHC, RT-PCR, TMA, HPLC | [49] | |
MAGE-A3 | Elevated levels can be found in early melanoma stages | May be elevated in other tumours Its use as a prognostic factor is not yet proven |
RT-PCR | [50][51] | |
Glycoprotein YKL-40 | Found to be an independent prognostic marker correlating with disease-free and overall survival | Has not received FDA authorisation Can yield false-negative results Can be associated with other tumours or inflammatory processes |
ELISA | [52][53][54][55][56] | |
CYT-MAA | Linked with disease recurrence and progression May be related to response to immunotherapy |
Not sensitive or specific | [57] | ||
MTF | Thought to contribute to angiogenesis, tumour proliferation | It is also excreted in exocrine tissues | ELISA, IHC, RT-PCR | [57][58][59][60] | |
MITF | Has a diagnostic role in melanoma Increased levels with reduced invasiveness |
Exact physiological role not yet discovered | ELISA, IHC, RT-PCR, HPLC | [61][62][64] | |
GP100 | Increased levels are found in neonatal cells and melanoma cells | Not specific Not proven to correlate with response to treatment |
ELISA, IHC, RT-PCR | [65][66][67] | |
CRP | Elevated CRP and IL6 are linked to reduced survival and treatment resistance CRP may be an independent predictor for survival |
Can also be elevated by a multitude of other factors | IP | [67][68][69] | |
S100 Proteins | S100 β | Increased levels with reduced survival May be related with disseminated disease Recommended in some German and Swiss guidelines as surveillance |
S100b can also be elevated in liver, brain, renal injury, inflammatory and infectious conditions | ELISA, LIA | [23][24][26][27][28] |